We have isolated two glycoproteins that bind to Con A and which immunolocalize exclusively to the membranes of the stratum corneum, and to the outermost cornified cells in primary cultures grown on floating collagen gels, implying that these are intrinsic epidermal molecules. We have identified putative precursors for each glycoprotein on Western blots of epidermal extracts. Interestingly, the precursors in the tissues are not labeled by the antibodies. The epidermis is similar to the stratified squamous epithelial lining various other organs. We are inclined to believe that the precursor molecules will be expressed by other epithelial such as palatal, gingival, and lingual mucosa, but the post- translational modification processes are different in that they do not normally keratinize. This will explain why under pathologic conditions, they are capable of keratinizing. So, we like to generate specific antibodies to the precursors, to localize them in the tissues. Ether-dispersed single corneocytes still express the two glycoproteins. We have been able to reconstitute a multi- layered "stratum corneum" from these corneocytes. The addition of the antibody to the 40 kD glycoprotein disrupted the reconstitution and thus plays an essential role in adhesion in the stratum corneum, and we suspect that the 30 kD glycoprotein does too. Because these proteins are not synthesized, as such, in the stratum corneum, we would like to study their biosynthesis in an organ culture system (as well as their modulation by retinoids). We want to generate monoclonal antibodies to the stratum corneum glycoproteins and their precursors which will enables us to identify the functionally significant domains of these molecules. The establishment of an in-vitro cell-free translation system, together with amino acid sequencing studies, will enable us in the future to search c-DNA libraries produced from epidermal cell m-RNA to study the gene expression and regulation of these molecules. The proposed studies will greatly enhance our understanding of the function of cell surface glycoproteins in cell adhesion and desquamation of the epidermis; and the pathobiological aspects of normal and abnormal differentiation pathways in oral diseases.